Methods comprising immobilizing a subject molecule (especially a low-molecular compound) to a solid phase support or binding the molecule to another molecule, and measuring a interaction of low-molecular compound and high-molecular compound, low-molecular compound and low-molecular compound or high-molecular compound and high-molecular compound, or purifying a target molecule on the basis of a specific interaction are used successfully in various fields. For example, target protein research using an affinity resin aiming at a novel drug discovery target search is known well. As representative examples of this research, the discovery of FKBP proteins, which bind to the immunosuppressant FK506 (FK506 inding proteins) using an affinity resin by Professor Schreiber in 1989 (discovery of FKBP12 as a protein that binds to FK506 in cells; see, for example, Nature, UK, Oct. 26, 1989, Vol. 341, pp. 758-760), the subsequently done discovery f calcineurin inhibitory action in the mechanism of harmacological action of FK506 by an FK506-FKBP complex (see, or example, Cell, USA, Aug. 23, 1991, Vol. 66, No. 4, pp. 807-815), the discovery of HDAC as a target protein for the anticancer agent Trapoxin (see, for example, Science, USA, Apr. 19, 1996, Vol. 272, pp. 408-411) and the like are known well.
However, to date, to immobilize a low-molecular compound to a solid phase support, it has been necessary to introduce a spacer selectively to a position where the activity is not affected in the low-molecular structure. For this reason, to conduct research for searching and purifying a target molecule, or for analyzing the interaction of a subject molecule and a target thereof, it has been essential to conduct a broad range of research into structure-activity correlation in the subject low-molecular compound in advance, so as to identify a site on the structure at which the desired activity is not lost. However, such investigation has required immense investments and time because it is necessary to synthesize a vast number of compounds separately from each starting material, and to measure the pharmacological activities thereof. Additionally, there are many cases where the desired compound cannot be obtained within the limited time span of research, including some cases where the target search is unavoidably abandoned. Accordingly, the essentially required research into structure-activity correlation has been a major hurdle against the conduct of the above-described research.
In recent years, large investments in genome-based drug discovery have been made for the purpose of effective drug discovery target search; since target search using an affinity resin permits more efficient investments than genome research, a new approach to overcoming the above-described drawback has been waited for.
It is an object of the present invention to provide a method that enables an analysis of intermolecular interactions on a solid phase support, without the need of research into structure-activity correlation, and a search of a target molecule for a subject compound (ligand) on the basis of the analysis.